β-차단제의 진정작용에 관한 검색

Abstract

β-遮斷劑의 發見은 交感神經系 收容體 學說의 理論的 根據를 提示하게 되었고 새로운 β-遮斷劑의 開發은 學述的 興味를 脫皮하여 臨床的으로 心循環系 疾患에 不可缺한 治療藥으로 脚光을 받게 되어 心不全症 및 高血壓症例에 크게 寄與하고 있다. 그뿐아니라 近者에는 副作用으로 看做되었던 β-遮斷劑의 中樞抑制作用이 不安症 특히 自律神經系緊張이 關與하는 體性不安症에 有效함이 指摘되자（Granville-Grossman 및 Turner, 1966） 이에 同調하는 斷片的 臨床報告가 提示되어 새로운 角度에서 β-遮斷劑의 效果가 注目받게 되었다. 이와 같은 β-遮斷劑의 效能은 文化發展에 따르는 異狀緊張을 解消하는데 至大한 도움이 되리라 믿으나 아직 系統的으로 評價된 實驗報告가 殆無하여 本 實驗에서 우선 代表的 β-遮斷劑인 propranolol과 最近에 出品됨2~3種 藥物을 使用하여 中樞鎭靜效果에 關한 檢索을 試圖하게 되었다. 著者는 토끼 및 병아리를 使用하여 propranolol을 위시한 β-遮斷劑의 中樞作用 特히 抗痙攣效果 및 thiopental 睡眠延長效果를 檢索하였고 2~3種 藥物의 效果와 比較하여 이에 報告하였다. 1. 병아리의 Strychnine 痙攣은 β-遮斷劑 前處置로 抑制되고 propranolol 및 pindolol 處置群에서 특히 抑制效果가 顯著하였다. 그러나 dichloroisoproterenol（DCI）및 酸棘仁은 strychnine 痙攣에 影響이 없을 뿐 아니라 DCI에서는 오히려 痙攣航進作用을 나타냈다. 2. 병아리의 pentylenetetrazol 痙攣은 β-遮斷劑 前處置로 別影響이 없고 도리어 pentylenetetrazol 大量投與로 因한 痙攣 實驗에서 致死率을 顯著히 增加시켰다. 다만 pindolol은 pentylenetetrazol 小量投與로 因한 痙攣을 diazepam 같이 效果的으로 沮止하였다. 3. 병아리의 電擊으로 因한 痙攣은 propranolol 處置로 그 期間이 顯箸히 短縮되었다. 4. 토끼의 thiopental 睡眠時間은 모든 β-遮斷劑로 顯箸히 延長되었다. 5. 酸棘仁은 pentylenetrazol 小量投與로 因한 병아리 痙攣을 效果的으로 抑制하였고, 토끼의 thiopental 睡眠時間을 意義있게 延長시켰다. Epinephrine 前處置는 興奮毒 痙攣과 thiopental 睡眠에 影響을 주지 않았다. 6. 토끼에서 propranolol로 因한 thiopental 睡眠時間 延長效果는 reserpine 前處置로 完全 沮止되고 tranylcypromine 前處置 動物에서는 오히려 短縮을 招來하였다. 以上의 結果로 보아 β-遮斷劑는 脊髓痙攣을 抑制하고 麻醉時間을 延長하나 痙攣으로 因한 致死率은 增加시킴을 알 수 있다. 이와같은 作用은 體內 catecholamine 含量 및 β-收容體活動과 關聯이 깊은 것으로 생각된다. ; Granville-Grossman and Turner（1966）were the first to suggest that beta-adrenoceptor blockade might be effective in the treatment of pathological anxiety. They found that only autonomically mediated symptoms were significantly improved by propranolol, but psychic anxiety, tension, and irritability were not. Some more recent reports support this view. Tyrer and Lader（1974）found in a crossover study that in 6 patients with chronic anxiety and mainly somatic symptoms and 6 more patients with mainly psychic symptoms given successively propranolol, diazepam, or placebo, patient preference and psychiatric rating favored diazepam for the whole group, but in the patients with somatic symptoms the responses to diazepam and propranolol were comparable. Present study was undertaken to delineate the effect of propranolol on central nervous system in chicks and rabbits, and the anticonvulsive and sedative effects of propranolol were compared with those having a highly potent β-adrenergic blocking property. The results are follows 1. In general, convulsion of chicks due to strychnine were inhibited by pretreatment with β-adrenergic blockers. Maked inhibitory effects were observed with propranolol and pindolol. Extracts of wild jujube seeds（Zizyphus vulgaris var. sponosus）, which has β-adrenergic blocking activities in other systems showed no effect on the strychnine convulsion. On the other hand the classical β-blocker, dichloroisoproterenol aggravated strychnine convulsion. 2. Pretreatments of chicks with β-adrenergic blockers had no significant effect on the convulsions due to pentylenetetrazol, however the pretrestments caused an increase in mortality due to pentylenetetrazol. Among the β-blockers tested, pindolol alone showed diazepam-like anticonvulsive effect against low dose of pentylenetetrazol. 3. Propranolol pretreatment caused a marked decrease in the duration of electric shock in chicks. 4. Zizyphus extract inhibited effectively the convulsion of chicks due to low doses of pentylenetetrazol, and caused a significant increase in thiopental sleeping time in rabbits. Epinephrine pretreatment had no effect on the pentylenetetrazol convulsion or the thiopental sleeping time. 5. In rabbits, pretreatments with β-adrenergic blockers caused a marked increase in thiopental sleeping time. 6. When rabbits were pretreated with tranlcypromine or reserpine one day prior to the experiments, propranolol no longer prolonged the thiopental sleeping time. On the contrary, the sleeping time was even shortened in the tranylcypromine treated animals. From the above observations, it may be tentatively concluded that β-adrenergic blocking agents inhibits spinal convulsions and prolong the duration of anesthesia, but cause an increase of mortality due to convulsion. It is believed that these effects have intimate relationships with catecholamine contents of various tissues and the functions of adrenergic receptors.